WO2000035906A2 - 4- et 5-alkynyloxindoles et 4- et 5-alcenyloxindoles - Google Patents

4- et 5-alkynyloxindoles et 4- et 5-alcenyloxindoles Download PDF

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Publication number
WO2000035906A2
WO2000035906A2 PCT/EP1999/009578 EP9909578W WO0035906A2 WO 2000035906 A2 WO2000035906 A2 WO 2000035906A2 EP 9909578 W EP9909578 W EP 9909578W WO 0035906 A2 WO0035906 A2 WO 0035906A2
Authority
WO
WIPO (PCT)
Prior art keywords
indol
dihydro
pyrrol
methylene
methoxy
Prior art date
Application number
PCT/EP1999/009578
Other languages
English (en)
Other versions
WO2000035906A3 (fr
Inventor
Kin-Chun Luk
Paige E. Mahaney
Steven Gregory Mischke
Original Assignee
F. Hoffmann-La Roche Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by F. Hoffmann-La Roche Ag filed Critical F. Hoffmann-La Roche Ag
Priority to CA002354510A priority Critical patent/CA2354510A1/fr
Priority to DE69912479T priority patent/DE69912479T2/de
Priority to AU15076/00A priority patent/AU771599B2/en
Priority to JP2000588166A priority patent/JP2002532490A/ja
Priority to EP99957341A priority patent/EP1149092B1/fr
Priority to BR9916272-5A priority patent/BR9916272A/pt
Priority to KR1020017007552A priority patent/KR20010087421A/ko
Priority to AT99957341T priority patent/ATE253062T1/de
Priority to DK99957341T priority patent/DK1149092T3/da
Publication of WO2000035906A2 publication Critical patent/WO2000035906A2/fr
Publication of WO2000035906A3 publication Critical patent/WO2000035906A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Abstract

L'invention concerne des 4- et 5-alkynyloxindoles ainsi que des 4- et 5-alcényloxindoles représentés par les formules (I) et (II), dans lesquelles R?1, R2, R3, R11, R12¿, X et z ont la signification indiquée dans la description. Ces composés inhibent ou modulent les protéines kinases, notamment les protéines kinases JNK, et ils sont utilisés comme agents anti-inflammatoires pour le traitement de la polyarthrite rhumatoïde notamment.
PCT/EP1999/009578 1998-12-17 1999-12-07 4- et 5-alkynyloxindoles et 4- et 5-alcenyloxindoles WO2000035906A2 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
CA002354510A CA2354510A1 (fr) 1998-12-17 1999-12-07 4- et 5-alkynyloxindoles et 4- et 5-alcenyloxindoles
DE69912479T DE69912479T2 (de) 1998-12-17 1999-12-07 4- und 5-alkynyloxindole sowie 4- und 5-alkenyloxindole
AU15076/00A AU771599B2 (en) 1998-12-17 1999-12-07 4- and 5-alkynyloxindoles and 4- and 5-alkenyloxindoles
JP2000588166A JP2002532490A (ja) 1998-12-17 1999-12-07 ４−および５−アルキニルオキシンドールと４−および５−アルケニルオキシンドール
EP99957341A EP1149092B1 (fr) 1998-12-17 1999-12-07 4- et 5-alkynyloxindoles et 4- et 5-alkenyloxindoles
BR9916272-5A BR9916272A (pt) 1998-12-17 1999-12-07 4 e 5-alquiniloxindóis e 4 e 5-alqueniloxindóis
KR1020017007552A KR20010087421A (ko) 1998-12-17 1999-12-07 4- 및 5-알키닐옥신돌과 4- 및 5-알케닐옥신돌
AT99957341T ATE253062T1 (de) 1998-12-17 1999-12-07 4- und 5-alkynyloxindole sowie 4- und 5- alkenyloxindole
DK99957341T DK1149092T3 (da) 1998-12-17 1999-12-07 4- og 5-alkynyloxindoler og 4- og 5-alkenyloxindoler

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US11258998P 1998-12-17 1998-12-17
US60/112,589 1998-12-17
US14148299P 1999-06-29 1999-06-29
US60/141,482 1999-06-29

Publications (2)

Publication Number Publication Date
WO2000035906A2 true WO2000035906A2 (fr) 2000-06-22
WO2000035906A3 WO2000035906A3 (fr) 2000-11-09

Family

ID=26810125

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/009578 WO2000035906A2 (fr) 1998-12-17 1999-12-07 4- et 5-alkynyloxindoles et 4- et 5-alcenyloxindoles

Country Status (14)

Country Link
EP (1) EP1149092B1 (fr)
JP (1) JP2002532490A (fr)
KR (1) KR20010087421A (fr)
CN (1) CN1147486C (fr)
AT (1) ATE253062T1 (fr)
AU (1) AU771599B2 (fr)
BR (1) BR9916272A (fr)
CA (1) CA2354510A1 (fr)
DE (1) DE69912479T2 (fr)
DK (1) DK1149092T3 (fr)
ES (1) ES2209527T3 (fr)
PT (1) PT1149092E (fr)
TR (1) TR200101747T2 (fr)
WO (1) WO2000035906A2 (fr)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002002551A1 (fr) * 2000-06-30 2002-01-10 Sugen, Inc. 4-heteroaryl-3-heteroarylidenyl-2-indolinones et leur utilisation comme inhibiteurs des proteine kinases
US6451838B1 (en) 2000-05-24 2002-09-17 Pharmacia & Upjohn Company 1-(pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
WO2002092065A2 (fr) * 2001-05-16 2002-11-21 Cephalon, Inc. Nouvelles methodes de traitement et de prevention de la douleur
WO2003032999A1 (fr) * 2001-10-12 2003-04-24 Warner-Lambert Company Llc Inhibiteurs de metalloproteinase matricielle (mmp) a base d'alkyne
US6569868B2 (en) 1998-04-16 2003-05-27 Sugen, Inc. 2-indolinone derivatives as modulators of protein kinase activity
US6599902B2 (en) 2001-05-30 2003-07-29 Sugen, Inc. 5-aralkysufonyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors
WO2003072550A1 (fr) * 2002-02-28 2003-09-04 Eisai Co., Ltd. Nouveaux composes indazole a anneaux fusionnes
US6706709B2 (en) 2000-06-02 2004-03-16 Sugen, Inc. Indolinone derivatives as protein kinase/phosphatase inhibitors
US6747147B2 (en) 2002-03-08 2004-06-08 Warner-Lambert Company Oxo-azabicyclic compounds
US6894057B2 (en) 2002-03-08 2005-05-17 Warner-Lambert Company Oxo-azabicyclic compounds
US6962922B2 (en) 2001-10-12 2005-11-08 Warner-Lambert Company Llc Alkynylated quinazoline compounds
US6982274B2 (en) 2001-04-16 2006-01-03 Eisai Co., Ltd. 1H-indazole compound
US7105563B2 (en) 2003-10-24 2006-09-12 Schering Aktiengesellschaft Indolinone derivatives and their use in treating disease-states such as cancer
US20080176900A1 (en) * 2005-09-27 2008-07-24 Hesheng Zhang 5H-THIOENO(3,4-c)PYRROLE-4,6-DIONE DERIVATIVES AND THEIR USE AS TUMOR NECROSIS FACTOR INHIBITORS
US7429609B2 (en) 2002-05-31 2008-09-30 Eisai R & D Management Co., Ltd. Pyrazole compound and medicinal composition containing the same
US7465736B2 (en) 2002-06-14 2008-12-16 Laboratoires Serono S.A. Azole methylidene cyanide derivatives and their use as protein kinase modulators
US7683078B2 (en) 2001-07-23 2010-03-23 Laboratoires Serono S.A. Arylsulfonamide derivatives as C-Jun-N-Terminal Kinases (JNK's) inhibitors
US7803824B2 (en) 2004-10-29 2010-09-28 Alcon, Inc. Use of inhibitors of Jun N-terminal kinases to treat glaucoma
EP2248521A1 (fr) 2004-10-29 2010-11-10 Alcon, Inc. Inhibiteurs de jun n-terminal kinases pour le traitement de la retinophatie glaucomateuse et de maladies oculaires
US7968572B2 (en) 2005-10-03 2011-06-28 Ono Pharmaceuticals Co., Ltd. Nitrogen-containing heterocyclic compound and pharmaceutical application thereof
WO2012178015A2 (fr) * 2011-06-24 2012-12-27 Zenobia Therapeutics, Inc. Inhibiteurs de lrrk2
US8592414B2 (en) 2005-07-15 2013-11-26 Merck Serono, S.A. JNK inhibitors for the treatment of endometriosis
US8658640B2 (en) 2005-07-15 2014-02-25 Merck Serono Sa JNK inhibitors for the treatment of endometriosis

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004012070A1 (de) * 2004-03-12 2005-09-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue cycloalkyl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel
WO2006090698A1 (fr) * 2005-02-22 2006-08-31 Ono Pharmaceutical Co., Ltd. Inhibiteur de kinases et utilisation de celui-ci
FR2962729B1 (fr) 2010-07-13 2012-09-21 Arkema France Molecules porteuses de groupes associatifs
FR2962733B1 (fr) 2010-07-13 2012-08-17 Michelin Soc Tech Polymere greffe par des molecules associatives azotees.
TWM609142U (zh) 2019-11-27 2021-03-11 財團法人工業技術研究院 發電感測傳輸裝置

Citations (5)

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WO1996022976A1 (fr) * 1995-01-26 1996-08-01 Pharmacia S.P.A. Derives hydrosolubles de 3-arylidene-2-oxindole utiles comme inhibiteurs de la kinase de tyrosine
WO1996032380A1 (fr) * 1995-04-07 1996-10-17 Pharmacia & Upjohn S.P.A. Analogues d'indolylmethylene-oxindole substitues en tant qu'inhibiteurs des tyrosines kinases
WO1996040116A1 (fr) * 1995-06-07 1996-12-19 Sugen, Inc. Composes d'indolinone pour le traitement de maladies
WO1997045409A1 (fr) * 1996-05-24 1997-12-04 Pharmacia & Upjohn, S.P.A. Analogues de tetralylmethylen-oxindole substitues utilises comme inhibiteurs de la tyrosine-kinase
WO1998050356A1 (fr) * 1997-05-07 1998-11-12 Sugen, Inc. Derives de 2-indolinone utilises en tant que modulateurs de l'activite de la proteine kinase

Family Cites Families (1)

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Publication number Priority date Publication date Assignee Title
AU4155697A (en) * 1996-08-23 1998-03-06 Sugen, Inc. Indolinone combinatorial libraries and related products and methods for the treatment of disease

Patent Citations (5)

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Publication number Priority date Publication date Assignee Title
WO1996022976A1 (fr) * 1995-01-26 1996-08-01 Pharmacia S.P.A. Derives hydrosolubles de 3-arylidene-2-oxindole utiles comme inhibiteurs de la kinase de tyrosine
WO1996032380A1 (fr) * 1995-04-07 1996-10-17 Pharmacia & Upjohn S.P.A. Analogues d'indolylmethylene-oxindole substitues en tant qu'inhibiteurs des tyrosines kinases
WO1996040116A1 (fr) * 1995-06-07 1996-12-19 Sugen, Inc. Composes d'indolinone pour le traitement de maladies
WO1997045409A1 (fr) * 1996-05-24 1997-12-04 Pharmacia & Upjohn, S.P.A. Analogues de tetralylmethylen-oxindole substitues utilises comme inhibiteurs de la tyrosine-kinase
WO1998050356A1 (fr) * 1997-05-07 1998-11-12 Sugen, Inc. Derives de 2-indolinone utilises en tant que modulateurs de l'activite de la proteine kinase

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6569868B2 (en) 1998-04-16 2003-05-27 Sugen, Inc. 2-indolinone derivatives as modulators of protein kinase activity
US6451838B1 (en) 2000-05-24 2002-09-17 Pharmacia & Upjohn Company 1-(pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
US6482848B2 (en) 2000-05-24 2002-11-19 Sugen Incorporated Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
US7112603B2 (en) 2000-05-24 2006-09-26 Agouron Pharmaceuticals, Inc. Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
US7053113B2 (en) 2000-05-24 2006-05-30 Sugen, Inc. Mannich base prodrugs of 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives
US7008943B2 (en) 2000-05-24 2006-03-07 Pharmacia & Upjohn Company 1-(Pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
US6716870B2 (en) 2000-05-24 2004-04-06 Sugen, Inc. Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
US6710067B2 (en) 2000-05-24 2004-03-23 Sugen Incorporated Mannich base prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
US6706709B2 (en) 2000-06-02 2004-03-16 Sugen, Inc. Indolinone derivatives as protein kinase/phosphatase inhibitors
US7071332B2 (en) 2000-06-02 2006-07-04 Sugen, Inc. Indolinone derivatives as protein kinase/phosphatase inhibitors
US7053086B2 (en) 2000-06-30 2006-05-30 Sugen, Inc. 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors
WO2002002551A1 (fr) * 2000-06-30 2002-01-10 Sugen, Inc. 4-heteroaryl-3-heteroarylidenyl-2-indolinones et leur utilisation comme inhibiteurs des proteine kinases
US6635640B2 (en) 2000-06-30 2003-10-21 Sugen, Inc. 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors
US6982274B2 (en) 2001-04-16 2006-01-03 Eisai Co., Ltd. 1H-indazole compound
US7541376B2 (en) 2001-04-16 2009-06-02 Eisai R&D Management Co., Ltd. 1H-indazole compounds
US7776890B2 (en) 2001-04-16 2010-08-17 Eisai R&D Management Co., Ltd. 1H-indazole compounds
WO2002092065A2 (fr) * 2001-05-16 2002-11-21 Cephalon, Inc. Nouvelles methodes de traitement et de prevention de la douleur
WO2002092065A3 (fr) * 2001-05-16 2003-07-31 Cephalon Inc Nouvelles methodes de traitement et de prevention de la douleur
US7018999B2 (en) 2001-05-16 2006-03-28 Cephalon, Inc. Methods for the treatment and prevention of pain
US6599902B2 (en) 2001-05-30 2003-07-29 Sugen, Inc. 5-aralkysufonyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors
US7683078B2 (en) 2001-07-23 2010-03-23 Laboratoires Serono S.A. Arylsulfonamide derivatives as C-Jun-N-Terminal Kinases (JNK's) inhibitors
US6849648B2 (en) 2001-10-12 2005-02-01 Warner-Lambert Company Phenylene alkyne matrix metalloproteinase inhibitors
US6962922B2 (en) 2001-10-12 2005-11-08 Warner-Lambert Company Llc Alkynylated quinazoline compounds
WO2003032999A1 (fr) * 2001-10-12 2003-04-24 Warner-Lambert Company Llc Inhibiteurs de metalloproteinase matricielle (mmp) a base d'alkyne
US7390797B2 (en) 2002-02-28 2008-06-24 Eisai Co., Ltd. Fused indazole compounds
WO2003072550A1 (fr) * 2002-02-28 2003-09-04 Eisai Co., Ltd. Nouveaux composes indazole a anneaux fusionnes
US6894057B2 (en) 2002-03-08 2005-05-17 Warner-Lambert Company Oxo-azabicyclic compounds
US6747147B2 (en) 2002-03-08 2004-06-08 Warner-Lambert Company Oxo-azabicyclic compounds
US7429609B2 (en) 2002-05-31 2008-09-30 Eisai R & D Management Co., Ltd. Pyrazole compound and medicinal composition containing the same
US7465736B2 (en) 2002-06-14 2008-12-16 Laboratoires Serono S.A. Azole methylidene cyanide derivatives and their use as protein kinase modulators
US7105563B2 (en) 2003-10-24 2006-09-12 Schering Aktiengesellschaft Indolinone derivatives and their use in treating disease-states such as cancer
US7803824B2 (en) 2004-10-29 2010-09-28 Alcon, Inc. Use of inhibitors of Jun N-terminal kinases to treat glaucoma
EP2248521A1 (fr) 2004-10-29 2010-11-10 Alcon, Inc. Inhibiteurs de jun n-terminal kinases pour le traitement de la retinophatie glaucomateuse et de maladies oculaires
US8592414B2 (en) 2005-07-15 2013-11-26 Merck Serono, S.A. JNK inhibitors for the treatment of endometriosis
US8658640B2 (en) 2005-07-15 2014-02-25 Merck Serono Sa JNK inhibitors for the treatment of endometriosis
US20080176900A1 (en) * 2005-09-27 2008-07-24 Hesheng Zhang 5H-THIOENO(3,4-c)PYRROLE-4,6-DIONE DERIVATIVES AND THEIR USE AS TUMOR NECROSIS FACTOR INHIBITORS
US8183260B2 (en) * 2005-09-27 2012-05-22 Tianjin Hemay Bio-Tech Co., Ltd. 5H-thioeno(3,4-c)pyrrole-4,6-dione derivatives and their use as tumor necrosis factor inhibitors
US7968572B2 (en) 2005-10-03 2011-06-28 Ono Pharmaceuticals Co., Ltd. Nitrogen-containing heterocyclic compound and pharmaceutical application thereof
WO2012178015A2 (fr) * 2011-06-24 2012-12-27 Zenobia Therapeutics, Inc. Inhibiteurs de lrrk2
WO2012178015A3 (fr) * 2011-06-24 2013-05-10 Zenobia Therapeutics, Inc. Inhibiteurs de lrrk2

Also Published As

Publication number Publication date
WO2000035906A3 (fr) 2000-11-09
DK1149092T3 (da) 2004-02-23
ATE253062T1 (de) 2003-11-15
ES2209527T3 (es) 2004-06-16
PT1149092E (pt) 2004-03-31
AU771599B2 (en) 2004-03-25
CN1331689A (zh) 2002-01-16
EP1149092A2 (fr) 2001-10-31
TR200101747T2 (tr) 2001-11-21
EP1149092B1 (fr) 2003-10-29
DE69912479T2 (de) 2004-07-22
KR20010087421A (ko) 2001-09-15
DE69912479D1 (de) 2003-12-04
CN1147486C (zh) 2004-04-28
JP2002532490A (ja) 2002-10-02
AU1507600A (en) 2000-07-03
CA2354510A1 (fr) 2000-06-22
BR9916272A (pt) 2001-09-04

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